Cifuentes-Mendiola Saúl Ernesto, Moreno-Fierros Leticia, González-Alva Patricia, García-Hernández Ana Lilia
Laboratory of Dental Research, Section of Osteoimmunology and Oral Immunology, FES Iztacala, National Autonomous University of Mexico, San Sebastián Xhala, Cuautitlán Izcalli 54714, Mexico.
Laboratory of Mucosal Immunity, FES Iztacala, National Autonomous University of Mexico, Los Reyes Iztacala, Tlalnepantla 54090, Mexico.
Exp Ther Med. 2022 Mar;23(3):235. doi: 10.3892/etm.2022.11160. Epub 2022 Jan 21.
Patients with type 2 diabetes mellitus (DM2) experience an increased risk of fractures and a variety of bone pathologies, such as osteoporosis. The suggested mechanisms of increased fracture risk in DM2 include chronic hyperglycaemia, which provokes oxidative stress, alters bone matrix, and decreases the quality of hydroxyapatite crystals. Docosahexaenoic acid (DHA), an omega-3 fatty acid, can increase bone formation, reduce bone loss, and it possesses antioxidant/anti-inflammatory properties. The present study aimed to determine the effect of DHA on altered osteoblast mineralisation and increased reactive oxygen species (ROS) induced by high glucose concentrations. A human osteoblast cell line was treated with 5.5 mM glucose (NG) or 24 mM glucose (HG), alone or in combination with 10 or 20 µM DHA. The collagen type 1 (Col1) scaffold, the expression of osteocalcin (OCN) and bone sialoprotein type-II (BSP-II), the alkaline phosphatase (ALP) specific activity, the mineral quality, the production of ROS and the mRNA expression of nuclear factor erythroid 2-related factor-2 (NRF2) were analysed. Osteoblasts cultured in HG and treated with either DHA concentration displayed an improved distribution of the Col1 scaffold, increased OCN and BSP-II expression, increased NRF2 mRNA, decreased ALP activity, carbonate substitution and reduced ROS production compared with osteoblasts cultured in HG alone. DHA counteracts the adverse effects of HG on bone mineral matrix quality and reduces oxidative stress, possibly by increasing the expression of NRF2.
2型糖尿病（DM2）患者发生骨折及各种骨病理状况（如骨质疏松症）的风险增加。DM2患者骨折风险增加的潜在机制包括慢性高血糖，它会引发氧化应激、改变骨基质并降低羟基磷灰石晶体的质量。二十二碳六烯酸（DHA）是一种ω-3脂肪酸，可促进骨形成、减少骨质流失，并且具有抗氧化/抗炎特性。本研究旨在确定DHA对高糖浓度诱导的成骨细胞矿化改变和活性氧（ROS）增加的影响。将人成骨细胞系分别用5.5 mM葡萄糖（正常血糖，NG）或24 mM葡萄糖（高血糖，HG）处理，单独处理或与10或20 μM DHA联合处理。分析了I型胶原蛋白（Col1）支架、骨钙素（OCN）和II型骨唾液蛋白（BSP-II）的表达、碱性磷酸酶（ALP）的比活性、矿物质质量、ROS的产生以及核因子红细胞2相关因子2（NRF2）的mRNA表达。与单独在HG中培养的成骨细胞相比，在HG中培养并用任一DHA浓度处理的成骨细胞显示出Col1支架分布改善、OCN和BSP-II表达增加、NRF2 mRNA增加、ALP活性降低、碳酸盐替代减少以及ROS产生减少。DHA可能通过增加NRF2的表达来抵消HG对骨矿物质基质质量的不利影响并减轻氧化应激。
